tbuckley/cabot-search huggingface dataset:
Abstract 295: Availability Of Automatic Defibrillators And Volunteer Responders For Out-of-hospital Cardiac Arrest In Denmark
Authors: Nanna B Christensen, Fredrik Folke, Julie S Kjoelbye, Christian Torp-Pedersen, Mads Christian Tofte Gregers, Anne Juul Grabmayr, Louise K Jakobsen, Kristian Bundgaard Ringgren, Linn Andelius, Carolina Malta Hansen
Journal: Circulation (2022)

Introduction: Public automatic defibrillators (AEDs) and bystander resuscitation (CPR) are critical for cardiac arrest survival. We examined how availability of AEDs and volunteer responders that can be summoned with an app have developed following many national initiatives to improve survival. Methods: All OHCA (Out-of-Hospital Cardiac Arrest) registered with coordinates within the Danish Cardiac Arrest Registry (2016-2020) were included. This study assessed coverage of 1) AEDs and 2) volunteer responders at 12 noon for home and public OHCAs. Coverage was defined as ≥ 1 AED and ≥ 4 volunteer responders within 200, 500, or 1,800 meters using straight line distance from the OHCA. Results: A total of 22,330 OHCAs were included. At 12 noon, 33,180 volunteer responders (572/100,000 inhabitants) and 22,418 AEDs (387/100,000 inhabitants) were available. More OHCA were covered with AEDs compared to volunteer responders for all distances. A significant difference was found in AED coverage in public compared to home arrests for all distances (p for difference at all distances &lt;0.05). Opposite, no difference was found in volunteer responder coverage for home compared to public arrests at 1,800 and 500 meters (p for difference &gt;0.05). Figure 1 illustrates AED and volunteer responder coverage for home and public arrest. Conclusion: Following the implementation of a national volunteer responder program and strategic placement of AEDs in Denmark, most historical OHCAs were covered by AEDs and volunteer responders within 1,800 meters. Although we have more volunteer responders per 100,000 inhabitants compared to AEDs, we found more than half (53%) of all OHCA were covered with AEDs within 200 meters whereas only 16% of all OHCAs were covered by volunteer responders within 200 meters. These findings indicate strategic AED placement in Denmark, but further efforts regarding volunteer responder recruitment are needed to increase coverage of the historical OHCA in Denmark.
Abstract 272: Withholding/withdrawal Of Life-sustaining Therapy Decision For Out-of-hospital Cardiac Arrest Patients With Extracorporeal Cardiopulmonary Resuscitation Is Commonly Influenced By Perceived Unfavorable Neurological Prognosis At Early Admission
Authors: Hiromichi Naito, Masaaki Sakuraya, Takashi Hongo, Tetsuya Yumoto, Atsunori Nakao
Journal: Circulation (2022)

Introduction: Extracorporeal cardiopulmonary resuscitation (ECPR) in patients with refractory cardiac arrest is rapidly becoming a common strategy worldwide. Despite its benefits, ECPR is still associated with significant morbidity, including a high prevalence of brain injury/ischemia. ECPR raises a variety of ethical concerns when discontinuing treatment, however, there is little information about the withholding/withdrawal of life-sustaining therapy (WLST) decision for out-of-hospital cardiac arrest (OHCA) patients after ECPR. Hypothesis: We tested whether early WLST is obtained in OHCA patients with ECPR, and examined the differences in patient characteristics between ECPR/OHCA patients with or without WLST. Methods: We conducted a post-hoc analysis of data from the SAVE-J II study (a retrospective, multicenter study of ECPR in Japan from 2013 to 2018). Inclusion criteria: Patients who underwent ECPR for OHCA with internal causes. Exclusion criteria: death in the emergency department (without admission), diagnosis of brain hemorrhage/acute aortic dissection as cause of arrest. The dates and reasons for the decisions were recorded. Further, differences between ECPR/OHCA patients with or without WLST were compared using univariable analysis. Results: We included 1651 patients in the analysis; WLST was decided in 506 (31%) of patients at a median of two days. WLST was decided within three days in 291 patients (18%). Reasons for WLST decision were perceived unfavorable neurological prognosis (285/477 [59.7%]), perceived unfavorable cardiac/pulmonary prognosis (99/477 [20.7%]), inability to maintain extracorporeal cardiopulmonary support (71/477 [14.8%]), complications (12/477 [2.5%]), and others (10/477 [2%]). Older age (WLST vs. non-WLST, median [IQR]: 63 [51-71] vs. 61 [49-68], p=0.001) and daily hemodialysis before the collapse (7.7% vs. 4.7%, p=0.015) were factors in the WLST decision. Patients with WLST had higher 1 month mortality (505/506 [99.8%] vs. 889/1145 [77.6%], p&lt;0.001). Conclusion: About one-third of ECPR/OHCA patients had WLST decided at a median of two days, mainly for perceived unfavorable neurological prognoses reason. Decisions and neurological assessments for ECPR/OHCA patients need further analysis.
Inhaled Technosphere Insulin Compared With Injected Prandial Insulin in Type 1 Diabetes: A Randomized 24-Week Trial
Authors: Bruce W. Bode, Janet B. McGill, Daniel L. Lorber, Jorge L. Gross, P.-C. Chang, David B. Bregman
Journal: Diabetes Care (2015)

OBJECTIVE To compare the efficacy and safety of Technosphere insulin (TI) and insulin aspart in patients with type 1 diabetes. RESEARCH DESIGN AND METHODS This open-label noninferiority trial compared the change in HbA1c from baseline to week 24 of prandial TI (n = 174) with that of subcutaneous aspart (n = 171), both with basal insulin, in patients with type 1 diabetes and HbA1c 7.5–10.0% (56.8–86.0 mmol/mol). RESULTS Mean change in HbA1c in TI patients (–0.21% [–2.3 mmol/mol]) from baseline (7.94% [63.3 mmol/mol]) was noninferior to that in aspart patients (–0.40% [–4.4 mmol/mol]) from baseline (7.92% [63.1 mmol/mol]). The between-group difference was 0.19% (2.1 mmol/mol) (95% CI 0.02–0.36), satisfying the noninferiority margin of 0.4%. However, more aspart patients achieved HbA1c &amp;lt;7.0% (53.0 mmol/mol) (30.7% vs. 18.3%). TI patients had a small weight loss (–0.4 kg) compared with a gain (+0.9 kg) for aspart patients (P = 0.0102). TI patients had a lower hypoglycemia event rate than aspart patients (9.8 vs. 14.0 events/patient-month, P &amp;lt; 0.0001). Cough (generally mild) was the most frequent adverse event (31.6% with TI, 2.3% with aspart), leading to discontinuation in 5.7% of patients. Treatment group difference for mean change from baseline in forced expiratory volume in 1 s was small (40 mL) and disappeared upon TI discontinuation. CONCLUSIONS In patients with type 1 diabetes receiving basal insulin, HbA1c reduction with TI was noninferior to that of aspart, with less hypoglycemia and less weight gain but increased incidence of cough.
Therapeutic Hypothermia after Cardiac Arrest
Authors: Peter J. Safar, Patrick M. Kochanek
Journal: New England Journal of Medicine (2002)

In this issue of the Journal, the reported results of two randomized clinical trials, one in Australia1 and the other in Europe,2 showed a neurologic benefit of mild therapeutic hypothermia (33°C in the first study and 32°C to 34°C in the second) in survivors of out-of-hospital cardiac arrest.3 In the Australian study, which involved a total of 77 patients who remained comatose after the restoration of spontaneous circulation, 49 percent of those treated with hypothermia were discharged home or to a rehabilitation facility, as compared with 26 percent of those not treated with hypothermia (P=0.046).1 There were no significant differences . . .
Clonal hematopoiesis is associated with protection from Alzheimer’s disease
Authors: Hind Bouzid, Julia A. Belk, Max Jan, Yanyan Qi, Chloé Sarnowski, Sara Wirth, Lisa Ma, Matthew R. Chrostek, Herra Ahmad, Daniel Nachun, Winnie Yao, Joshua Bis, Bruce Psaty, Alexa Beiser, Alexander G. Bick, Joshua C. Bis, Myriam Fornage, William T. Longstreth, Oscar L. Lopez, Pradeep Natarajan, Bruce M. Psaty, Claudia L. Satizabal, Joshua Weinstock, Eric B. Larson, Paul K. Crane, C. Dirk Keene, Sudha Seshadri, Ansuman T. Satpathy, Thomas J. Montine, Siddhartha Jaiswal
Journal: Nature Medicine (2023)

Abstract Clonal hematopoiesis of indeterminate potential (CHIP) is a premalignant expansion of mutated hematopoietic stem cells. As CHIP-associated mutations are known to alter the development and function of myeloid cells, we hypothesized that CHIP may also be associated with the risk of Alzheimer’s disease (AD), a disease in which brain-resident myeloid cells are thought to have a major role. To perform association tests between CHIP and AD dementia, we analyzed blood DNA sequencing data from 1,362 individuals with AD and 4,368 individuals without AD. Individuals with CHIP had a lower risk of AD dementia (meta-analysis odds ratio (OR) = 0.64, P = 3.8 × 10 −5 ), and Mendelian randomization analyses supported a potential causal association. We observed that the same mutations found in blood were also detected in microglia-enriched fraction of the brain in seven of eight CHIP carriers. Single-nucleus chromatin accessibility profiling of brain-derived nuclei in six CHIP carriers revealed that the mutated cells comprised a large proportion of the microglial pool in the samples examined. While additional studies are required to validate the mechanistic findings, these results suggest that CHIP may have a role in attenuating the risk of AD.
Sequential and directional insulation by conserved CTCF sites underlies the Hox timer in stembryos
Authors: Hocine Rekaik, Lucille Lopez-Delisle, Aurélie Hintermann, Bénédicte Mascrez, Célia Bochaton, Alexandre Mayran, Denis Duboule
Journal: Nature Genetics (2023)

During development, Hox genes are temporally activated according to their relative positions on their clusters, contributing to the proper identities of structures along the rostrocaudal axis. To understand the mechanism underlying this Hox timer, we used mouse embryonic stem cell-derived stembryos. Following Wnt signaling, the process involves transcriptional initiation at the anterior part of the cluster and a concomitant loading of cohesin complexes enriched on the transcribed DNA segments, that is, with an asymmetric distribution favoring the anterior part of the cluster. Chromatin extrusion then occurs with successively more posterior CTCF sites acting as transient insulators, thus generating a progressive time delay in the activation of more posterior-located genes due to long-range contacts with a flanking topologically associating domain. Mutant stembryos support this model and reveal that the presence of evolutionary conserved and regularly spaced intergenic CTCF sites controls the precision and the pace of this temporal mechanism.
Effects of urban living environments on mental health in adults
Authors: Jiayuan Xu, Nana Liu, Elli Polemiti, Liliana Garcia-Mondragon, Jie Tang, Xiaoxuan Liu, Tristram Lett, Le Yu, Markus M. Nöthen, Jianfeng Feng, Chunshui Yu, Andre Marquand, Gunter Schumann, Henrik Walter, Andreas Heinz, Markus Ralser, Sven Twardziok, Nilakshi Vaidya, Emin Serin, Marcel Jentsch, Esther Hitchen, Roland Eils, Ulrike-Helene Taron, Tatjana Schütz, Kerstin Schepanski, Jamie Banks, Tobias Banaschewski, Karina Jansone, Nina Christmann, Andreas Meyer-Lindenberg, Heike Tost, Nathalie Holz, Emanuel Schwarz, Argyris Stringaris, Maja Neidhart, Frauke Nees, Sebastian Siehl, Ole A. Andreassen, Lars T. Westlye, Dennis van der Meer, Sara Fernandez, Rikka Kjelkenes, Helga Ask, Michael Rapp, Mira Tschorn, Sarah Jane Böttger, Gaia Novarino, Lena Marr, Mel Slater, Guillem Feixas Viapiana, Francisco Eiroa Orosa, Jaime Gallego, Alvaro Pastor, Andreas Forstner, Per Hoffmann, Markus M. Nöthen, Andreas J. Forstner, Isabelle Claus, Abbi Miller, Stefanie Heilmann-Heimbach, Peter Sommer, Mona Boye, Johannes Wilbertz, Karen Schmitt, Viktor Jirsa, Spase Petkoski, Séverine Pitel, Lisa Otten, Anastasios-Polykarpos Athanasiadis, Charlie Pearmund, Bernhard Spanlang, Elena Alvarez, Mavi Sanchez, Arantxa Giner, Sören Hese, Paul Renner, Tianye Jia, Yanting Gong, Yunman Xia, Xiao Chang, Vince Calhoun, Jingyu Liu, Paul Thompson, Nicholas Clinton, Sylvane Desrivieres, Allan H. Young, Bernd Stahl, George Ogoh
Journal: Nature Medicine (2023)

Abstract Urban-living individuals are exposed to many environmental factors that may combine and interact to influence mental health. While individual factors of an urban environment have been investigated in isolation, no attempt has been made to model how complex, real-life exposure to living in the city relates to brain and mental health, and how this is moderated by genetic factors. Using the data of 156,075 participants from the UK Biobank, we carried out sparse canonical correlation analyses to investigate the relationships between urban environments and psychiatric symptoms. We found an environmental profile of social deprivation, air pollution, street network and urban land-use density that was positively correlated with an affective symptom group ( r = 0.22, P perm &lt; 0.001), mediated by brain volume differences consistent with reward processing, and moderated by genes enriched for stress response, including CRHR1 , explaining 2.01% of the variance in brain volume differences. Protective factors such as greenness and generous destination accessibility were negatively correlated with an anxiety symptom group ( r = 0.10, P perm &lt; 0.001), mediated by brain regions necessary for emotion regulation and moderated by EXD3 , explaining 1.65% of the variance. The third urban environmental profile was correlated with an emotional instability symptom group ( r = 0.03, P perm &lt; 0.001). Our findings suggest that different environmental profiles of urban living may influence specific psychiatric symptom groups through distinct neurobiological pathways.
Abstract 159: Time-course Of Left Ventricular Systolic Dysfunction Recovery After Cardiac Arrest
Authors: Rachel Beekman, Noah Kim, Kamil Faridi, Ehimen Aneni, Tiffany E Chang, Andrew Arakaki, Eva Kitlen, Elliott Miller, Akhil Khosla, Charles R Wira, David M Greer, emily j gilmore
Journal: Circulation (2022)

Introduction: Myocardial dysfunction is a well-documented feature of post-cardiac arrest syndrome. The natural history of left ventricular systolic dysfunction (LVSD) remains largely unknown. We sought to characterize the change in left ventricular systolic function after return of spontaneous circulation (ROSC). Methods: This is a retrospective review of cardiac arrest patients at a single tertiary center between 2015 and 2020. We included patients with a transthoracic echocardiogram (TTE) documenting left ventricular ejection fraction (EF) within 1 day of ROSC and at least one follow-up TTE within 6 months after cardiac arrest. LVSD was defined as EF &lt;40% on TTE. Patients with known LVSD preceding cardiac arrest were excluded. Using paired t-test, we compared initial (within 1 day of ROSC) and follow up TTEs, stratified by shockable rhythm status. Recovery of LVSD was defined as improvement in EF to &gt;50%. Results: Of 477 cardiac arrest patients, 89 (18.7%) patients met the inclusion criterion. 28 (31.5%) had a baseline TTE on file; 5 patients had LVSD prior to arrest and were excluded, leaving a cohort of 84 patients. Thirty-one (36.9%) patients had LVSD on TTE after ROSC, of which 16 (51.6%) had recovery of EF on follow up TTE. The figure shows the timeline of EF recovery for the whole cohort. In-hospital follow up TTE (n=84) was done at a median (IQR) of 7 (4,16) days and post-discharge follow up (n=26) at 63 (29, 115) days. In patients with shockable rhythm arrest, EF improved from ROSC to inpatient follow up TTE [mean (SD) 36% (2.6) to 50% (2.5), P &lt;0.001]. Patients with non-shockable rhythm arrest had a higher baseline EF with a non-significant change at follow up [50% (2.6) to 56% (2.5), p=0.072]. Conclusion: Among survivors of cardiac arrest, significant recovery of LVSD was common. Further work is necessary to elucidate predictors of myocardial recovery and to determine optimal timing for repeat echocardiography.
Abstract 14520: Paradoxical Increase in Myeloperoxidase Inhibitory Capacity Associated With Poorer Outcomes in Acute Cardio-Renal Syndrome
Authors: Joseph Mauch, Timothy Engelman, Wai Hong W Tang
Journal: Circulation (2022)

Introduction: While implicated in both cardiac and renal dysfunction, it remains unclear if myeloperoxidase (MPO) plays a role in the development of acute cardiorenal syndrome (CRS). We developed an assay to quantify MPO inhibitory capacity (MIC) to assess a plasma sample’s capacity to inhibit MPO activity. Hypothesis: We hypothesized that unopposed MPO activity (less inhibition) contributes to development of acute CRS and greater MPO inhibition leads to improved clinical outcomes. Methods: 90 paired samples of acute heart failure (AHF) patients were collected at enrollment and between 24-96 hours follow-up. Diluted samples were supplemented with 100 ng/mL exogenous MPO and allowed to equilibrate for 1 hour at room temperature. Equal parts sample and Amplex UltraRed Reagent were incubated for 30 minutes, and fluorescence was read. 59 patients had long-term follow-up data for time to readmission survival analysis, censored for loss to follow up, death, or transplantation. Results: Patients with CRS have higher rather than lower MIC compared to that in uncomplicated patients (50% vs 34%, p=0.048). Serial MIC measurements during hospitalization revealed that patients with persistently low MIC experienced better outcomes (median time to readmission 575 days vs 104 days, p=0.023, Figure). Conclusions: Contrary to our original hypothesis, we observed acute CRS patients had higher rather than lower MIC, and that persistently low MIC experienced better long-term outcomes. These results imply that in patients experiencing acute CRS, there is a circulating MPO inhibitory component that has not been previously accounted for, and that unopposed MPO activity was not associated with CRS or poor outcomes.
Abstract 15269: Late Recovery of Left Ventricular Function After Surgical Aortic Valve Replacement for Severe Aortic Regurgitation
Authors: Yan Naung Htay, Su Sandi Aung, Prabhakaran Gopalakrishnan, Ryan Koene
Journal: Circulation (2022)

Introduction: Surgical aortic valve replacement (SAVR) is recommended in symptomatic severe aortic regurgitation (AR) or asymptomatic severe AR with reduced left ventricular (LV) ejection fraction (LVEF). Although most patients have improvement in LV dimensions and LVEF early (&lt; 6 months) after SAVR, severe baseline LV enlargement and reduced LVEF, along with persistent LV dilation after SAVR, carries a worse prognosis. We present a case in which a patient with these features had complete recovery of LVEF late (&gt; 9 months) after SAVR for severe AR. Case Description: A healthy 62-year-old male presented with dyspnea and chest pain. Cardiac workup was significant for ECG showing left bundle branch block; both transthoracic and trans-esophageal echocardiograms showed bicuspid aortic valve with severe AR (Eccentric jet, pressure half time (PHT): 221 msec, jet width &gt; 60% of LV outﬂow tract diameter), severely reduced LVEF 20-25%, and severe LV dilation (LVESD of 75 mm), and cardiac catheterization showed mild coronary disease. SAVR was performed without complications and heart failure therapy initiated. Patient declined cardiac resynchronization therapy. The LVEF and LVESD were persistently abnormal in TTE at 5 and 9 months. The TTE at 21 months showed normalization, with LVEF of 55% and LVESD of 46 mm, despite no prior improvement (Figure). Discussion: In severe AR following SAVR, volume overload reduction results in LV size reduction and improved LVEF, usually within a few months and in those with smaller baseline LV dimensions. Some studies suggest a specific LV dimension to perform SAVR. This report indicates that SAVR should not be excluded based on severe LV dilation alone. Conclusion: The incidence and mechanisms of delayed reverse cardiac remodeling in severe AR after SAVR and optimal timing of decision about device placement needs further investigation.
Abstract 15293: Predictive Value of Thyroid Hormone Levels in Patients Suffering From Cardiogenic Shock Complicating Acute Myocardial Infarction
Authors: Michael Buerke, Priyanka Boettger
Journal: Circulation (2022)

Hypothesis: Introduction. Acute critically ill patients experience a rapid decline in plasma free thyroid hormone levels (free triiodothyronine (FT3) and free levothyroxine (FT4)), with a marked elevation of reverse T3, recognized as the euthyroid sick syndrome (ESS) or low-T3 syndrome. The ESS is also often associated with depressed myocardial function, sometimes referred to as the 'stunned myocardium. The role of thyroid hormone levels in patients with cardiogenic shock complicated myocardial infarction has not been shown Methods: The purpose of the study was to assess the impact of thyroid hormone levels on hospital mortality in patients with infarction related cardiogenic shock. Thyroid hormone levels were measured from routine blood specimens and analyzed initial and up to 96 hours. Results: We identified 40 patients with infarction related cardiogenic shock treated at our university hospital. Majority of the CS-patients had on admission reduced TSH levels of 1,42 ± 0,22mU/l. Nevertheless, in-hospital mortality rate was higher in patients with lower admission TSH levels and levels over time. In addition, FT3 in CS-survivors showed a flat slope from normal levels. Non-survivor had a trend towards lower levels after 72 and 96 hours. When we analyzed for low T3 syndrome (i.e. FT3 &gt;3,1pmol/l) we saw a 3x times higher mortality rate compared to CS patients with normal levels. In contrast, FT4 levels of non survivors were significantly elevated compared to surviving CS patients. After 96 hours both groups had similar levels. Predictors of hospital death in CS patients were low TSH levels, low T3 syndrome and elevated FT4. Conclusions: Thyroid hormone level on admission and over time (i.e. low TSH, low T3 and elevated FT4) are predictors of in-hospital death in patients with infarction related cardiogenic shock. Interestingly TSH stays almost stable over time whereas FT3 and FT4 declines over time. Further studies have to show if administration of thyroid hormone might be beneficial in patients with infarction related cardiogenic shock.